1304 results about "Dimer" patented technology

Bispecific antibodies comprising (a) a first light-heavy chain pair having specificity for a first target and a sufficient number of substitutions in its heavy chain constant domain with respect to a corresponding wild-type antibody of the same isotype to significantly reduce the formation of first heavy chain-first heavy chain dimers and (b) a second light-heavy chain pair comprising a heavy chain having a sequence that is complementary to the sequence of the first pair heavy chain sequence with respect to the formation of intramolecular ionic interactions, wherein the first pair or second pair comprises a substitution in the light chain and complementary substitution in the heavy chain that reduces the ability of the light chain to interact with the heavy chain of the other light chain-heavy chain pair are provided. Methods of producing such antibodies in one or more cells also are provided.

The invention provides methods for simultaneously amplifying multiple nucleic acid regions of interest in one reaction volume as well as methods for selecting a library of primers for use in such amplification methods. The invention also provides library of primers with desirable characteristics, such as minimal formation of amplified primer dimers or other non-target amplicons.

Some aspects of this disclosure provide compositions, methods, and kits for improving the specificity of RNA-programmable endonucleases, such as Cas9. Also provided are variants of Cas9, e.g., Cas9 dimers and fusion proteins, engineered to have improved specificity for cleaving nucleic acid targets. Also provided are compositions, methods, and kits for site-specific recombination, using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to a recombinase catalytic domain). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.

The present invention concerns methods and compositions for stably tethered structures of defined compositions, which may have multiple functionalities and/or binding specificities. Particular embodiments concern homodimers comprising monomers that contain a dimerization and docking domain attached to a precursor. The precursors may be virtually any molecule or structure, such as antibodies, antibody fragments, antibody analogs or mimetics, aptamers, binding peptides, fragments of binding proteins, known ligands for proteins or other molecules, enzymes, detectable labels or tags, therapeutic agents, toxins, pharmaceuticals, cytokines, interleukins, interferons, radioisotopes, proteins, peptides, peptide mimetics, polynucleotides, RNAi, oligosaccharides, natural or synthetic polymeric substances, nanoparticles, quantum dots, organic or inorganic compounds, etc. Other embodiments concern tetramers comprising a first and second homodimer, which may be identical or different. The disclosed methods and compositions provide a facile and general way to obtain homodimers, homotetramers and heterotetramers of virtually any functionality and/or binding specificity.

Compounds of Formula (Ia)

wherein R is a C₆-C₁₂ substituted or unsubstituted aryl, a C₆-C₁₂ substituted or unsubstituted heteroaryl, a C₁-C₆ substituted or unsubstituted alkyl or —NR′R′,

• Q is C(O), O, NR′, S, S(O)₂, C(O)₂ (CH2)p
• Y is C(O), O, NR′, S, S(O)₂, C(O)₂ (CH2)_p
• Z is H or C₁-C₄ alkyl,
• R′ is H, C(O), S(O)₂, C(O)₂, a C₆-C₁₂ substituted or unsubstituted aryl, a C₆-C₁₂ substituted or unsubstituted heteroaryl or a C₁-C₆ substituted or unsubstituted alkyl, when substituted, aryl, heteroaryl and alkyl are substituted with halogen, C₆-C₁₂ heteroaryl, —NR′R′ or COOZ, which have diagnostic and therapeutic properties, such as the treatment and management of prostate cancer and other diseases related to NAALADase inhibition. Radiolabels can be incorporated into the structure through a variety of prosthetic groups attached at the X amino acid side chain via a carbon or hetero atom linkage.

The invention provides methods for simultaneously amplifying multiple nucleic acid regions of interest in one reaction volume as well as methods for selecting a library of primers for use in such amplification methods. The invention also provides library of primers with desirable characteristics, such as minimal formation of amplified primer dimers or other non-target amplicons.

The invention relates to single-chain multimeric polypeptides comprising at least two units of a monomeric polypeptide linked via a peptide bond or a peptide linker, wherein the monomeric polypeptide is of a type that is biologically active in monomeric form, and to polypeptide conjugates having at least one non-polypeptide moiety covalently bound to an attachment group of the polypeptide. The polypeptide is preferably a G-CSF dimer bound to a polymer molecule, preferably to one or more polyethylene glycol molecules.

The invention provides chimeric proteins having at least two functional protein units, each containing the dimerization domain of a member of the steroid/thyroid hormone nuclear receptor superfamily. The chimeric proteins can fold under crystallization conditions to form functional entities. The functional entities optionally contain a novel flexible peptide linker of variable lengths between at least two of the protein units. In a preferred embodiment, the linker is designed to be increased in increments of 12 amino acids each to aid in preparation of variant chimeric proteins. The DNA binding characteristics of the invention functional entities differ from those of wild-type complexes formed between “monomeric” receptors and their binding partners. Some functional entities, e.g. dimers expressed as fusion proteins, transactivate responsive promoters in a manner similar to wild-type complexes, while others do not promote transactivation and function instead essentially as constitutive repressors. The invention further provides nucleotide sequences encoding the invention chimeric proteins, cells containing such nucleotide sequences, and methods for using the invention chimeric proteins to modulate expression of one or more exogenous genes in a subject organism. In addition, isolated protein crystals suitable for x-ray diffraction analysis and methods for obtaining putative ligands for the invention chimeric proteins are provided.

A process is provided for preparing organofunctional silanes, inclusive of dimers and oligomers, in which individual silanes possess both free and blocked mercaptan functionality or particular mixtures of the organofunctional silanes possess both free and blocked mercaptan functionality. The organofunctional silanes and silane mixtures are useful, inter alia, as coupling agents for elastomeric compositions, e.g., rubber formulations employed in the manufacture of tires, where they exhibit a desirable balance of low scorch and good performance properties.

The invention provides methods for simultaneously amplifying multiple nucleic acid regions of interest in one reaction volume as well as methods for selecting a library of primers for use in such amplification methods. The invention also provides library of primers with desirable characteristics, such as minimal formation of amplified primer dimers or other non-target amplicons.

The invention discloses a C3/C3 fluoroquinolone dimmer derivative using oxadiazole as a connection chain as well as a preparation method and an application thereof. The C3/C3 fluoroquinolone dimmer derivative using oxadiazole as a connection chain is a compound which has the following structural general formula (I), wherein R1 and R1' are independently selected from H, (C1-C10) alkyl, (C3)-(C10) cycloalkyl, (C1)-(C10) haloalkyl and substituted aryl group or substituted heterocyclic aryl group; R2 and R2' are independently selected from H, (C1-C7)alkyl, (C3)-(C7) cycloalkyl, substituted aryl group, substituted heterocyclic aryl group and hydrocarbon acyl or sulfonyl; R3 and R3' are independently selected from H, (C1-C5) alkyl, (C3)-(C5) cycloalkyl, substituted aryl radical or substitutionalheterocyclic aryl radical; and X and Y are independently selected from CH, N or carbon atoms connected with halogen, alkyl, oxyl, sulfenyl, amino, substituted amino, substituted aryl radical or substituted heterocyclic aryl radical. The C3/C3 fluoroquinolone dimmer derivative using oxadiazole as a connection chain can be used for preparing medicaments for treating tumors and preventing microbialinfection diseases.

Antibody capable of mediating effector function which specifically binds to a multiple membrane spanning antigen or to an antigen which forms dimers or multimers (i) for use in combination with a cholesterol-increasing agent in the treatment of a disease or disorder associated with said antigen, wherein antibody-induced effector function has a beneficial effect on said disease or disorder or (ii) for use in the treatment of such disease or disorder, wherein the antibody is to be administered to a subject undergoing therapy with a cholesterol-lowering agent, such as a statin, and wherein the subject is withdrawn from treatment with the cholesterol-lowering agent prior to the administration of the antibody. Furthermore, a kit of parts comprising such antibody as well as a cholesterol-increasing agent.

The present invention describes novel immunoglobulin compositions that co-engage at least two antigens, e.g. a first and second antigen, or, as outlined herein, three or four antigens can be bound, in some of the scaffold formats described herein. First and second antigens of the invention are herein referred to as antigen-1 and antigen-2 respectively (or antigen-3 and antigen-4, if applicable. As outlined herein, a number of different formats can be used, with some scaffolds relying combinations of monovalent and bivalent bindings.

The present invention relates to methods and compositions for symptom-based differential diagnosis, prognosis, and determination of treatment regimens in subjects. In particular, the invention relates to the use of biomarkers, either individually or in combinations with one another to rule in or out diseases of the aorta and its branches, most particularly aortic aneurysm and/or aortic dissection, and for risk stratification in such conditions. Preferred markers include one or more of creatine kinase-BB (CK-BB), creatine kinase-MB (CK-MB), acidic calponin, basic calponin, B-type natriuretic peptide (BNP), NT-proBNP, proBNP, BNP_79-108, BNP_3-108, caldesmon, caspase-3, D-dimer, soluble elastin fragments, endothelial cell-selective adhesion molecule (ESAM), fibrillin-1, heart-type fatty acid binding protein, MMP-9, myeloperoxidase, myoglobin, smooth muscle myosin, smooth muscle myosin heavy chain, TIMP-1, free cardiac troponin I, complexed cardiac troponin I, free and complexed cardiac troponin I, free cardiac troponin T, complexed cardiac troponin T, and free and complexed cardiac troponin T, and preferred assays are configured to detect these markers.

The invention relates to certain pyrrolobenzodiazepines (PBDs), and in particular pyrrolobenzodiazepine dimers bearing C2 substitutions, including compounds of formula (T): wherein: R² is CHR^2A, and R^2A is independently selected from H, R, CO₂R, COR, CHO, CO₂H, and halo; R⁶ and R⁹ are independently selected from H, R, OH, OR, SH, SR, NH₂, NHR, NRR′, NO₂, Me₃Sn and halo; R⁷ is independently selected from H, R, OH, OR, SH, SR, NH₂, NHR, NRR′, NO₂, Me₃Sn and halo; R⁸ is independently selected from H, R, OH, OR, SH, SR, NH₂, NHR, NRR′, NO₂, Me₃Sn and halo; R is independently selected from optionally substituted C_1-12 alkyl, C_3-20 heterocyclyl and C_5-20 aryl groups; or the compound is a dimer with each monomer being of formula (M), where the R⁷ groups or R⁸ groups of each monomer form together a dimer bridge having the formula —X—R″—X— linking the monomers; wherein R″ is a C_3-12 alkylene group, which chain may be interrupted by one or more heteroatoms, e.g. O, S, N(H), and/or aromatic rings, e.g. benzene or pyridine; and each X is independently selected from O, S, or N(H); or any pair of adjacent groups from R⁶ to R⁹ together form a group —O—(CH₂)_p—O—, where p is 1 or 2, and salts and solvates thereof, and their use as intermediates for the preparation of other PBD compounds.